Hyperpolarized 129Xe MRI for imaging NK cell therapy of lung metastasis

超极化 129Xe MRI 用于肺转移的 NK 细胞治疗成像

• 批准号: 10646013
• 负责人: James A Bankson
• 金额: $ 18.93万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10646013
• 关键词: Address; Adoptive Transfer; Affect; Allogenic; Anatomy; Animals; Antigens; Biodistribution; Biopsy; Cell Culture Techniques; Cell Therapy; Cells; Cellular immunotherapy; Chemicals; Child; Childhood Cancer Treatment; Clinic; Clinical; Development; Erythrocytes; Excision; FDA approved; Fluorocarbons; Foundations; Gases; Goals; Image; Imaging Device; Immune; Immunotherapy; Infusion procedures; Inhalation; Kinetics; Label; Logistics; Lung; Magnetic Resonance Imaging; Malignant Neoplasms; Metastatic Neoplasm to the Lung; Methods; Modality; Modeling; Monitor; NK cell therapy; Natural Killer Cell Immunotherapy; Natural Killer Cells; Neoplasm Metastasis; Patients; Phase I Clinical Trials; Physiology; Plasma; Positron-Emission Tomography; Protocols documentation; Radiation; Radiation Dose Unit; Recurrence; Refractory; Reporting; Resolution; Respiratory physiology; Safety; Sensitivity and Specificity; Solid Neoplasm; Structure of parenchyma of lung; T-Lymphocyte; Technology; Therapeutic; Time; Tissues; Tracer; Treatment Failure; Validation; Visualization; Water; absorption; amphiphilicity; anatomic imaging; biomedical imaging; cancer therapy; cellular imaging; clinical translation; cost; cytotoxicity; density; detection sensitivity; electronic cigarette use; feasibility testing; imaging approach; imaging biomarker; imaging modality; immune imaging; improved; in vivo; innovation; insight; interest; iron oxide nanoparticle; lung imaging; metabolic imaging; migration; mortality; nanoDroplet; non-invasive imaging; novel strategies; nuclear imaging; osteosarcoma; pediatric patients; respiratory gas; respiratory imaging; response; serial imaging; soft tissue; success; superparamagnetism; translatable strategy; tumor; volunteer

Abstract. Emerging cell-based therapies may greatly improve therapeutic success of cancer treatment. NK cell immunotherapy is particularly important in treatment of pediatric cancers, where information on tumor immunogens is lacking. Recently, there has been increased interest in the use of adoptive transfer of ex-vivo expanded NK cells for the treatment of solid tumors due to their innate features, higher safety compared to T cells and lower cost. This emerging therapy is of particular importance in osteosarcoma where 30-35% of patients die of pulmonary metastases due to a treatment-failure rate of 85% in this patient group. However, an important problem with implementation of cell therapies in the clinic is our inability to readily assess the presence and distribution of therapeutic cells after administration. Visualization of immune cell distribution and migration with non-invasive imaging could offer significant new insight into the progression of immunotherapy between infusion and invasive biopsy or resection. Although there are a number of viable approaches for imaging of immunotherapy, all current strategies have limitations and no technology has been proven as a single solution for longitudinal imaging of cellular immunotherapies. Therefore, it is important to continue pushing the limits of available imaging tools in order to find solutions that would address the pressing clinical needs. Hyperpolarized (HP) 129Xe MRI has recently emerged as a promising modality for direct imaging of respiratory function and gas absorption. Spectral separation between HP 129Xe gas in the airspace, tissue/plasma, and red blood cells permits quantification of gas absorption and exchange. Further, a few exploratory studies have demonstrated that chemical exchange saturation transfer (CEST) of HP 129Xe in perfluorocarbon nanodroplets (PFC NDs) can significantly enhance sensitivity to the presence of PFC ND’s due to a strong chemical shift between 129Xe gas in PFC and water. We see these developments as a tremendous opportunity to develop clinically translatable strategy for imaging NK cell therapy in the lungs. Here we propose to develop foundation for HP 129Xe CEST (hyperCEST) MRI of NK cells in vivo. The secondary goal is identification of imaging biomarkers of functional HP 129Xe MRI that may provide additional insight into response to cell immunotherapy. We will rely on our extensive expertise in (i) synthesis and applications of PFC NDs in biomedical imaging including cell labeling, and (ii) quantitative MRI, multinuclear imaging (13C, 19F, 129Xe) and metabolic imaging. Our hypothesis is that labeling of NK cells with PFC NDs optimized for 129Xe hyperCEST MRI will not adversely affect their functionality and will allow non-invasive NK cell monitoring with high sensitivity and specificity in the lungs. At the completion of these studies we will have a combination of optimized and validated probes for NK cell 129Xe hyperCEST MRI with corresponding imaging protocols that will provide foundation for further development of this promising technology towards clinical translation.

抽象的。新兴的基于细胞的疗法可能会极大地提高癌症治疗的成功率。NK细胞 免疫疗法在儿童癌症的治疗中尤为重要，在儿童癌症治疗中，有关肿瘤的信息 缺乏免疫原。近年来，体外领养转移的应用越来越受到人们的关注。 扩增的NK细胞因其固有的特性用于实体瘤的治疗，与T细胞相比安全性更高 电池和更低的成本。这种新出现的疗法对骨肉瘤尤其重要，在骨肉瘤中，30%-35%的患者 在这组患者中，治疗失败率为85%，死于肺转移。然而，一个重要的问题是 在临床上实施细胞疗法的问题是我们不能容易地评估存在和 给药后治疗细胞的分布情况。免疫细胞分布和迁移的可视化 非侵入性成像可以为免疫治疗的进展提供重要的新视角 和侵入性活组织检查或切除。虽然有许多可行的方法来成像 免疫疗法，所有目前的策略都有局限性，没有一种技术被证明是单一的解决方案 用于细胞免疫疗法的纵向成像。因此，继续挑战极限很重要 现有的成像工具，以便找到能够满足紧迫临床需求的解决方案。超极化 (惠普)129Xe磁共振成像最近已经成为一种很有前途的呼吸功能和气体直接成像方法 吸收。空气中HP 129Xe气体、组织/血浆和红细胞之间的光谱分离 气体吸收和交换的量化。此外，一些探索性研究已经证明 HP 129Xe在全氟碳纳米液滴中的化学交换饱和转移(CEST) 由于129Xe气体之间的强烈化学位移，显著提高了对PFC-ND存在的敏感性 在PFC和水中。我们认为这些进展是开发临床可翻译的巨大机会。 肺部NK细胞治疗的成像策略。在这里，我们建议为HP 129Xe CEST开发基础 活体NK细胞的高CEST磁共振成像。第二个目标是鉴定功能性的成像生物标记物。 HP 129Xe MRI，可为细胞免疫治疗的反应提供额外的洞察力。我们将依靠我们的 在(I)PFC NDS的合成和在生物医学成像中的应用包括细胞标记方面的广泛专业知识， (Ii)定量MRI、多核成像(13C、19F、129Xe)和代谢成像。我们的假设是 用针对129Xe HyperCEST MRI优化的PFC NDS标记NK细胞不会对其功能产生不利影响 并将允许在肺部进行具有高灵敏度和特异度的非侵入性NK细胞监测。在完成时 在这些研究中，我们将有针对NK细胞129Xe HyperCEST MRI的优化和验证探针的组合 以及相应的成像协议，将为进一步开发这一有前景的 面向临床翻译的技术。